H1N1 vaccine and the burden of proof

I am following with great interest all of the reports, both scientific and popular, on the reluctance to subject oneself to the H1N1 vaccine. Yesterday's WaPo reported that

A nationally representative poll of 1,042 adults released Friday by the Harvard School of Public Health found that only 40 percent were sure they would receive the vaccine and that about half were certain their children would. Recent research by the University of Michigan and by Consumer Reports yielded similar results.

Similarly, a CBS story reported that

Outside New York 's capitol building, health care workers - shouting "Give me liberty!" - vowed to fight an unprecedented order from state health officials: a requirement for every health care worker to get seasonal and H1N1 flu shots or face the possibility of being fired.

By some strange coincidence, the CBS story reports that, in any given year, the rate of voluntary vaccination against seasonal flu among healthcare workers is 40%. This begs the question: What is it about flu vaccination that engenders skepticism in over one-half of the population, whether healthcare professionals or lay people? And further, upon whom does the burden of proof in this argument fall? That is, does the government, who is mandating universal vaccination among NY healthcare providers, need to prove safety and efficacy to the satisfaction of the people or do the protesters need to prove to the government that their concerns are legitimate?

Let's take safety and efficacy. The mere fact that the vaccine has been approved by the FDA (and other regulatory bodies around the globe) should give us some comfort about its profile. Of course, we are all too aware of the recent debacles of removal of medications from the market due to safety signals, Vioxx being the most memorable of all. This drug, having undergone the FDA's scrutiny, was approved and then pulled because of an unacceptably high rate of cardiac events detected in treated patients in post-marketing studies. This has unquestionably colored the public's attitude toward drugs, even those receiving the FDA's blessing.

But is there something special about vaccines? From where I stand, vaccines are subject to an exaggerated suspicion on the part of the public, more so than other therapies. Well, my guess is that because most of the time the population for these injections consists of young and healthy individuals, the risk-benefit balance has to be much more weighted to the benefit side. What I mean is that the more seriously ill the person is, the more risk we are willing to accept for a small incremental benefit. Take cancer chemotherapy: when the alternative is certain death without a drug, the often severe side effects of that drug are acceptable given that it improves one's survival odds. Not so among the young and healthy. It would be absurd to accept the same risk profile from a vaccine that we would in a chemotherapy drug. OK, so there is the risk-benefit profile.

One important question that goes mostly unaddressed in safety discussions is that of time. That is, risk-benefit over what period of time? The flu vaccines, whether seasonal or H1N1, are developed annually and over a fairly contracted timeline. Can we possibly fathom the potential long-term risks of these vaccines in someone who is 20 years old today? Our drug approval process gives us a false comfort in that it only examines drug profiles in the short term. However, the human body is a complex network, and an exposure today may not make itself known until 20 or 30 years from now -- look at cigarettes and cancer. Further complicating this issue are several factors. First, we do not have a great system in the US for tracking adverse events, be it from drugs or from vaccines. The systems are voluntary, and for this reason incomplete and fraught with bias. Second, the task of connecting the potential exposure to an outcome separated by 20 or 30 years is a highly complex cognitive exercise. This task is made even more challenging if the exposure rate to the agent in question, here the vaccine, is very high. Under these circumstances, it may be difficult or impossible to connect the outcome to the exposure causally.

So, where does the burden of proof lie? The fact that even healthcare professionals have a hard time understanding this balance speaks to the complexity of the issue. As for the H1N1 mandatory vaccination of the healthcare workers, the added potential risk to the society may make the explicit risk-benefit balance easier to derive, given the immediacy of the outcomes. Nonetheless, I go back to my previous assertion that there is a dire need for better individual risk-benefit communication -- decision scientists and behavioral economists need to be recruited in droves to help with these dilemmas; we have the technology! In the long term, however, nothing will replace an educated consumer who is empowered to participate in this nuanced exercise.